The objective of the overall research in this laboratory is centered on achieving as complete a description as possible for the structures of peptides, proteins, nucleic acids and their complexes in solution, principally by NMR spectroscopy. At present particular emphasis is being placed on developing approaches which allow the investigation of larger and complex systems as well as increase the precision with which these solution structures can be obtained, studies aimed at correlating structure and function, and experiments aimed at investigating protein folding. Structures for several proteins have been determined and analyzed. These include the oligomerization domain of p53, a complex of human thioredoxin with its target site from the transcription actor NFkB, the DNA binding domain of Mu transposase, the DNA binding domain of HIV-1 integrase, and the specific complex of human SRY (the male sex determining factor) with DNA. The latter provides the molecular basis for understanding mutations in SRY that lead to 46X,Y sex reversal. Studies on protein hydration have revealed the presence of conformationally disordered water within a large l00-l20_3 internal hydrophobic cavity of interleukin-1b. In addition, work on the unfolded state of Streptococcal Protein G is continuing and the structure and dynamics of the unfolded State have been characterized by NMR.